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Long-term treatment with dopamine leads to motor complications such as dyskinesia. This indicates that after repeated dopaminergic stimulation, there may be changes in the response of the neuron to the same stimulus. The concept that dopamine transmission can modify the cellular cytoskeleton is novel and not yet well explored. The present study investigates how dopamine transmission is able to influence the cytoskeleton by studying the striatal Tau protein. Our results on the ex vivo side indicate that stimulation of dopamine receptors modifies Tau by altering its phosphorylation via glutamate receptors. On the in vivo side, we demonstrated that dopamine has a tonic effect on Tau phosphorylation and that denervation of dopaminergic neurons is an essential condition to induce changes in the cytoskeleton. This work has allowed us to highlight new molecular mechanisms in dopaminergic transmission during pathological dopaminergic conditions as seen in Parkinson's disease.